A5024892680- Immune Cell Function and Interaction
- Cancer Immunotherapy and Biomarkers
- Immune cells in cancer
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Neuroinflammation and Neurodegeneration Mechanisms
- Glioma Diagnosis and Treatment
- Pluripotent Stem Cells Research
- Peptidase Inhibition and Analysis
- Tissue Engineering and Regenerative Medicine
- Adenosine and Purinergic Signaling
- Mesenchymal stem cell research
Massachusetts General Hospital
2024
Harvard University
2024
Massachusetts Institute of Technology
2024
Center for Cancer Research
2024
Broad Institute
2023-2024
Duke University
2021-2022
Abstract Glioblastoma (GBM) is notorious for its immunosuppressive tumor microenvironment (TME) and refractory to immune checkpoint blockade (ICB). Here, we identify calmodulin-dependent kinase 2 (CaMKK2) as a driver of ICB resistance. CaMKK2 highly expressed in pro-tumor cells associated with worsened survival patients GBM. Host CaMKK2, specifically, reduces promotes Multimodal profiling the TME reveals that several resistance-associated phenotypes. exhaustion CD8 + T expansion effector CD4...
Abstract T cell-based therapies have transformed cancer treatment, although intrinsic or acquired resistance develops in nearly half of the patients. Tumor-infiltrating CD8+ lymphocytes (TILs) are key determinants anti-tumor immunity by secretion cytotoxic granules, such as granzymes and perforin, effector cytokines, TNFa IFNg. A deep understanding how TILs eliminate cells will help identify mechanisms develop new therapeutic strategies. Here, we demonstrate that eliminated matched melanoma...
Abstract Major Histocompatibility Complex (MHC) Class I downregulation is a well described mechanism of tumor immune escape, posing challenge for T cell based immunotherapies including checkpoint blockade (ICB). Recent studies, however, have demonstrated mixed roles MHC 1 and the critical component beta-2-microglobulin (β2m) expression in cancer progression ICB response, with some studies showing inactivation antigen presentation to be associated resistance others low β2m favorable...
<h3>Background</h3> Cancer immunotherapy with immune checkpoint blockade (ICB) has transformed the treatment of melanoma, although resistance is common and fatal. Tumor-infiltrating CD8+ T lymphocytes (TILs) are key determinants ICB response, strategies to enhance tumor cell sensitivity TILs an emerging approach overcome resistance. <h3>Methods</h3> We developed a patient-derived cancer cells co-culture system. To identify cell-intrinsic genes/pathways critical for TIL-mediated killing TILs,...
Abstract MHC-I downregulation is a well described mechanism of tumor immune escape. Thus, targeting tumors with low or no expression remains significant challenge for T cell-based immunotherapies, including checkpoint blockade (ICB). We previously demonstrated that the combination PD-1 and 4-1BB agonism has marked efficacy against intracranial murine CT2A glioma in CD8 cell-dependent manner. Surprisingly, this therapy remained effective β2 microglobulin knockout line overexpressing TRP2...
Abstract Objective: Glioblastoma is the most common and aggressive primary brain tumor with a 5 year prognosis of less than 5% survival. Efforts to extend this survival through therapeutic advancement have only led modest improvements. Immunotherapy has shown promise in other cancers but limited effect GBM, partially due dense infiltration pro-tumor myeloid cells. Calmodulin-dependent Kinase 2 (CaMKK2) highly expressed cells high expression associated more severe grade worse GBM. Preliminary...